ALDH1A3

Chr 15AR

aldehyde dehydrogenase 1 family member A3

Also known as: ALDH1A6, ALDH6, MCOP8, RALDH3

The protein catalyzes the NAD-dependent oxidation of retinal to retinoic acid, which is critical for embryonic development of the eye and nasal region. Autosomal recessive mutations cause isolated microphthalmia type 8, affecting ocular development. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.511), consistent with its essential role in early embryonic eye formation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.511 OMIM phenotype
Clinical SummaryALDH1A3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.51LOEUF
pLI 0.141
Z-score 3.31
OE 0.26 (0.140.51)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.24Z-score
OE missense 0.64 (0.570.72)
192 obs / 301.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.26 (0.140.51)
00.351.4
Missense OE0.64 (0.570.72)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 6 / 23.2Missense obs/exp: 192 / 301.2Syn Z: 0.07
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveALDH1A3-related anophthalmia/microphthalmiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.76top 25%
GOF
0.6735th %ile
LOF
0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ALDH1A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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